ALK-rearrangement in non-small-cell lung cancer (NSCLC)

Thorac Cancer. 2018 Apr;9(4):423-430. doi: 10.1111/1759-7714.12613. Epub 2018 Feb 28.

Abstract

The ALK gene encodes a transmembrane tyrosine kinase receptor. ALK is physiologically expressed in the nervous system during embryogenesis, but its expression decreases postnatally. ALK first emerged in the field of oncology in 1994 when it was identified to fuse to NPM1 in anaplastic large-cell lymphoma. Since then, ALK has been associated with other types of cancers, including non-small-cell lung cancer (NSCLC). More than 19 different ALK fusion partners have been discovered in NSCLC, including EML4, KIF5B, KLC1, and TPR. Most of these ALK fusions in NSCLC patients respond well to the ALK inhibitor, crizotinib. In this paper, we reviewed fusion partner genes with ALK, detection methods for ALK-rearrangement (ALK-R), and the ALK-tyrosine kinase inhibitor, crizotinib, used in NSCLC patients.

Keywords: ALK-rearrangement (ALK-R); ALK-tyrosine kinase inhibitor (TKI); anaplastic lymphoma kinase (ALK); detection platforms; non-small-cell lung cancer (NSCLC).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anaplastic Lymphoma Kinase / antagonists & inhibitors
  • Anaplastic Lymphoma Kinase / genetics*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Cycle Proteins / genetics
  • Crizotinib / therapeutic use
  • Drug Resistance, Neoplasm / genetics
  • Humans
  • Kinesins / genetics
  • Microtubule-Associated Proteins / genetics
  • Nuclear Pore Complex Proteins / genetics
  • Nucleophosmin
  • Oncogene Proteins, Fusion / genetics*
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins / genetics
  • Serine Endopeptidases / genetics

Substances

  • Cell Cycle Proteins
  • KIF5B protein, human
  • KLC1 protein, human
  • Microtubule-Associated Proteins
  • NPM1 protein, human
  • Nuclear Pore Complex Proteins
  • Oncogene Proteins, Fusion
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • TPR protein, human
  • Nucleophosmin
  • Crizotinib
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • EML4 protein, human
  • Serine Endopeptidases
  • Kinesins